What are the differentials and treatment options for conjunctivitis?

Differential Diagnosis of Conjunctivitis

The differential diagnosis of conjunctivitis must first distinguish true conjunctivitis from vision-threatening conditions, then categorize into infectious (viral, bacterial, chlamydial, gonococcal) versus noninfectious (allergic, mechanical, toxic, immune-mediated, neoplastic) etiologies, with the critical recognition that dry eye and blepharitis are the most frequent underlying causes of chronic conjunctival inflammation. 1

Primary Classification Framework

Infectious Conjunctivitis

Viral Conjunctivitis

• Adenoviral conjunctivitis presents with abrupt onset, initially unilateral becoming sequentially bilateral within days, watery discharge, follicular reaction on inferior tarsal conjunctiva, preauricular lymphadenopathy, and potential subconjunctival hemorrhages 2, 1
• Self-limited course with improvement within 5-14 days, though severe cases may develop subepithelial corneal infiltrates, conjunctival scarring, symblepharon, and lacrimal stenosis 2
• Herpes simplex virus (HSV) typically presents unilaterally with watery discharge, mild follicular reaction, and distinctive vesicular rash or ulceration of eyelids with excavated dendritic epithelial keratitis 2
• Varicella zoster virus (VZV) shows unilateral presentation with vesicular dermatomal rash, severe pain, and nonexcavated pseudodendritic keratitis 2
• Molluscum contagiosum causes chronic follicular conjunctivitis with distinctive shiny, dome-shaped umbilicated lesions on eyelid skin or margin 2

Bacterial Conjunctivitis

• Distinguished by mucopurulent discharge with matted eyelids on waking and papillary rather than follicular reaction 1
• Mattering and adherence of eyelids on waking, lack of itching, and absence of prior conjunctivitis history are strongest predictive factors 3
• Gonococcal conjunctivitis requires urgent recognition with marked eyelid edema, severe hyperpurulent discharge, rapid progression, and high risk of corneal infiltrate/ulcer beginning superiorly that may perforate 2, 1
• Chlamydial (inclusion) conjunctivitis in adults shows follicular conjunctivitis with distinctive follicles on bulbar conjunctiva and semilunar fold, while neonates present without follicles but with purulent or blood-stained discharge 2, 1
• Chlamydial (trachoma) caused by serotypes A, B, C presents with chronic follicular reaction, corneal pannus, and represents the leading infectious cause of global blindness 2

Parinaud Oculoglandular Syndrome

• Unilateral granulomatous follicular conjunctivitis with ipsilateral regional lymphadenopathy (preauricular and submandibular), most commonly from cat scratch disease (Bartonella henselae) or tularemia (Francisella tularensis) 2

Noninfectious Conjunctivitis

Allergic Conjunctivitis

• Affects up to 40% of the population with itching as the most consistent sign, bilateral presentation, eyelid edema, periorbital hyperpigmentation, and watery discharge with mild mucous component 1, 3
• Seasonal acute conjunctivitis commonly associated with rhinitis forming allergic rhinoconjunctivitis 4
• More severe forms include vernal keratoconjunctivitis and atopic keratoconjunctivitis requiring specialized ophthalmology follow-up 4

Mechanical/Irritative Causes

• Giant papillary conjunctivitis (GPC) shows papillary hypertrophy of superior tarsal conjunctiva with mucoid discharge, associated with contact lens wear (especially soft lenses with infrequent replacement, prolonged wearing time, poor hygiene) or exposed sutures 2
• Floppy eyelid syndrome presents with upper eyelid easily everted, horizontal lid laxity, diffuse papillary reaction of superior tarsal conjunctiva, associated with obesity, sleep apnea, and thyroid disease 2
• Conjunctival chalasis shows redundant conjunctiva with eyelid margin overhang that may occlude inferior puncta, associated with previous eye surgery and dry eye 2

Toxic/Medication-Induced

• Medication-induced/preservative-induced keratoconjunctivitis presents with conjunctival injection, punctal edema, inferior fornix and bulbar conjunctival follicles, keratitis (especially inferonasal), and contact dermatitis of eyelids 2
• Most common with topical glaucoma medications, NSAIDs, antibiotics, antivirals, and preservatives in eye medications 2
• Dupilumab-associated ocular surface disease shows bilateral conjunctival and limbal injection with watery or mucous discharge, presenting within weeks to months of dupilumab initiation 2

Immune-Mediated Conditions

• Ocular mucous membrane pemphigoid (OMMP) presents bilaterally (often asymmetric) with bulbar conjunctival injection, papillary conjunctivitis, subepithelial fibrosis, progressive conjunctival scarring beginning in fornices, symblepharon, and potential corneal perforation 2
• More common in women over age 60 with unknown etiology 2

Deficiency Disease

• Ligneous conjunctivitis caused by plasminogen deficiency (PLG gene) presents with chronic recurrent conjunctivitis and thick, firm/woody pseudomembranous structures on palpebral conjunctiva, 50% bilateral 2, 1

Neoplastic Conditions

• Conjunctival lymphoma appears as unilateral, painless, pink "salmon patch" fleshy conjunctival swelling, often with chronic palpebral or bulbar follicles, associated with immune deficiency and autoimmune conditions 2
• Ocular surface squamous neoplasia shows conjunctival hyperemia with papillomatous or sessile nodules, associated with HPV and UV exposure 2
• Sebaceous gland carcinoma presents with intense bulbar conjunctival injection, conjunctival scarring, may resemble chalazion with hard nodular nonmobile tarsal mass 2
• Melanoma appears as painless flat or nodular brown or white-pink lesion on bulbar/palpebral conjunctiva or caruncle 2

Underlying Ocular Surface Disease

• Dry eye and blepharitis are the most frequent causes of conjunctival inflammation and require treatment directed at the underlying problem rather than the conjunctivitis itself 1
• Giant fornix syndrome in elderly women (eighth to tenth decade) shows enlarged superior fornix with coagulum of mucopurulent material, chronic mucopurulent conjunctivitis that waxes and wanes 2

Critical Red Flags Requiring Immediate Ophthalmology Referral

Immediate referral is mandatory for: visual loss or decreased vision, moderate or severe pain, severe purulent discharge (especially gonococcal), corneal involvement, conjunctival scarring, lack of response to therapy, recurrent episodes, history of HSV eye disease, immunocompromised state, recent ocular surgery, vesicular rash on eyelids or nose, and neonatal conjunctivitis 1, 5

Diagnostic Approach

History must specifically assess: duration of symptoms (acute vs. chronic), character of discharge (watery vs. mucopurulent vs. mucoid), unilateral vs. bilateral presentation, presence of itching (strongly suggests allergic), concurrent upper respiratory infection (suggests viral), contact lens wear, medication use including eye drops, sexual history for chlamydia/gonorrhea risk, and systemic symptoms 1, 6

Physical examination must evaluate: conjunctival injection pattern (diffuse vs. localized), type of discharge, presence of follicles (viral, chlamydial) vs. papillae (bacterial, allergic), preauricular lymphadenopathy (viral, Parinaud), eyelid findings (vesicles, umbilicated lesions, laxity), and corneal involvement with fluorescein staining 1, 6

Treatment Algorithm by Etiology

Viral Conjunctivitis Management

• Self-limited requiring only supportive care with artificial tears and cold compresses for symptomatic relief 1, 7
• Patient education about high contagiousness and strict hand hygiene is essential to prevent transmission 1, 7
• Topical antibiotics are not indicated prophylactically but only if secondary bacterial infection develops 7
• HSV and VZV require local and systemic virostatic therapy when cornea or other ocular structures are affected 7

Bacterial Conjunctivitis Management

• Uncomplicated cases are self-limiting, resolving in 1-2 weeks without treatment 3, 5
• Topical broad-spectrum antibiotics (such as gatifloxacin 0.5% one drop every 2 hours while awake up to 8 times on day 1, then 2-4 times daily on days 2-7) decrease duration and allow earlier return to school/work 8, 3
• Delayed antibiotic prescribing has similar symptom control as immediate prescribing 5
• Gonococcal conjunctivitis requires urgent systemic treatment in addition to topical antibiotics 1, 3
• Chlamydial conjunctivitis requires systemic treatment and evaluation/treatment of sexual partners 1, 3

Allergic Conjunctivitis Management

• Topical antihistamines with mast cell-stabilizing activity are first-line treatment 1, 3, 4
• Preferably use single-dose or preservative-free formulations with dual action 4
• Allergen avoidance and lacrimal substitutes as non-pharmacological measures 4
• Short-lasting local steroid therapy reserved for severe flare-ups under specialized follow-up 4
• Cyclosporine as disease-modifying treatment for severe cases 4

Mechanical/Toxic Conjunctivitis Management

• Giant papillary conjunctivitis: discontinue contact lens wear, improve lens hygiene, or remove exposed sutures 2
• Medication-induced: discontinue offending agent, switch to preservative-free formulations 2
• Floppy eyelid syndrome: address underlying sleep apnea, consider surgical lid tightening 2

Common Pitfalls to Avoid

Avoid indiscriminate use of topical antibiotics or corticosteroids which may lead to unnecessary side effects, development of resistant organisms, and delayed diagnosis of underlying conditions 1, 6

Chronic and/or recalcitrant conjunctivitis may indicate underlying malignancy (lymphoma, squamous neoplasia, sebaceous carcinoma) and requires further evaluation including biopsy 1

Failing to recognize dry eye and blepharitis as the most frequent causes of chronic conjunctival inflammation leads to inadequate treatment focused on conjunctivitis rather than the underlying problem 1

Contact lens wearers with bacterial conjunctivitis should be treated with antibiotics due to risk of serious complications, unlike uncomplicated bacterial conjunctivitis in non-lens wearers 3

Patients should not wear contact lenses during bacterial conjunctivitis or during treatment 8